title: Poly(anhydride) administration in high doses in vivo: studies of biocompatibility and toxicology.
abstract: Poly(anhydrides) proposed for use as vehicles for controlled drug delivery were administered subcutaneously in Sprague-Dawley rats at two dosage levels (800 mg/kg rat and 2400 mg/kg rat) for a period of eight weeks. Biocompatibility was assessed using a number of methods. Thirty-six clinical chemistry and hematology parameters were monitored throughout the study. Blood values were statistically analyzed for any possible effects due to the implanted polymer. After 8 weeks, rats were sacrificed and complete necropsies were performed. Histological evaluations of 33 organ sites including heart, lung, liver, kidney, and brain were performed. In addition, subcutaneous implant sites were excised and examined both grossly and microscopically. Results from evaluations of blood chemistry and hematology data, organ analyses and local implant site analyses overall demonstrated that the poly(anhydride) biomaterial possessed excellent in vivo biocompatibility.
authors.affiliation: Harvard-M.I.T., Division of Health Sciences and Technology, Cambridge, Massachusetts.
authors.forename: C
authors.initials: C
authors.lastname: Laurencin
authors.forename: A
authors.initials: A
authors.lastname: Domb
authors.forename: C
authors.initials: C
authors.lastname: Morris
authors.forename: V
authors.initials: V
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Chasin
authors.forename: R
authors.initials: R
authors.lastname: McConnell
authors.forename: N
authors.initials: N
authors.lastname: Lange
authors.forename: R
authors.initials: R
authors.lastname: Langer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000633:toxicity*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D003238:Connective Tissue / Q000473:pathology; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D008422:Materials Testing; D011108:Polymers / Q000008:administration & dosage / Q000633:toxicity*; D019736:Prostheses and Implants; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D004343:Drug Implants; D011108:Polymers